The purpose of this proposal is to develop an approach which will elucidate the nature of the biochemical defects in human chromosomal aneuploid diseases. Specific genes of clinical importance will be identified on particular human chromosomes. Because it is associated with a well discribed aneuploid human disorder, Down Syndrome, human trisomy-21 furnishes an ideal model system for initiation of such studies. Using human-hamster hybrid cells containing human chromosome 21, protein mapping by two-dimensional SDS-polyacrylamide electrophoresis with dual radiosotope autography and identification of cell surface antigens due to genes on this chromosome will be carried out. Deletion mutant cells containing a fragment of chromosome 21 will be used to regionally map proteins and cell surface antigens whose genes are coded for by the chromosome, and to determine those genes which are not and those which may be concerned with the portion of chromosome 21 responsible for Down Syndrome. The gene products which appear to be associated with Down Syndrome will be then studied to determine their nature and possible role in the pathogenesis of Down Syndrome. Moreover, the logic and methods employed in these studies can then be used to analyze the role of other human chromosomes in disease.